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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 55 records · Page 3Linked to original sources
PubMed2004

[Diagnosis and treatment of autoimmune thyroiditis].

In Germany, autoimmune thyroiditis usually manifests as atrophic thyroiditis with functional hypothyroidism affecting elderly women in particular. Sonography and thyroid peroxidase antibodies (TPO antibodies) point the way to the diagnosis. Manifest hypothyroidism always requires substitution with levothyroxine. Many patients with subclinical hypothyroidism, especially those with positive thyroid antibodies, benefit from at least partial thyroxine substitution. Early treatment not only alleviates the clinical symptoms, but may possibly also diminish the associated cardiovascular risk. In pregnant and sterile women subclinical hypothyroidism should always be treated.

Adult↗
PubMed2004

[Drug-induced headache and pain reduction medication with amitriptyline in an 11-year old pupil].

We report on an 11-year-old pupil who present-ed to a neurological practice in the company of his parents because of migraine and strong headaches. Precise anamnesis of drugs yielded the diagnosis of a drug-induced headache with underlying migraine disease. The boy was afflict-ed with a hereditary taint, as both parents also suffered from migraine. The mother was also continuously in treatment because of a chronic pain disorder. Therapy with up to 50 mg per day of amitriptyline enabled the boy to stop consuming analgesics without suffering from head-aches. Moreover, under 47.5 mg per day of metoprolol, the migraine symptoms did not re-occur.

Amitriptyline↗
PubMed2004

Effects of a combination of recombinant human growth hormone with metformin on glucose metabolism and body composition in patients with metabolic syndrome.

Abdominal obesity and insulin resistance are central findings in metabolic syndrome. Since treatment with recombinant human growth hormone (rhGH) can reduce body fat mass in patients with organic GH deficiency, rhGH therapy may also have favourable effects on patients with metabolic syndrome. However, due to the highly increased risk for type 2 diabetes in these patients, strategies are needed to reduce the antagonistic effect of rhGH against insulin. We conducted a 18-month randomised, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (Met) in patients with metabolic syndrome. 25 obese men (55 +/- 6 years, BMI 33.4 +/- 2.9 kg/m (2)) with mildly elevated fasting plasma glucose (FPG) levels at screening (6.1-8.0 mmol/l) were included. All patients received metformin (850 mg twice daily) either alone or in combination with rhGH (daily dose 9.5 microg/kg body weight). An oGTT was performed at baseline, after 6 weeks, and after 3, 6, 12, and 18 months of therapy. Glucose disposal rate (GDR) was measured by euglycemic hyperinsulinemic clamp at 0 and 18 months and body composition was measured by DEXA every 6 months. In the Met + GH group, IGF-I increased from 146 +/- 56 microg/l to 373 +/- 111 microg/l (mean +/- SD) after 3 months and remained stable after that. BMI did not change significantly in either group during the study. Total body fat decreased by -4.3 +/- 5.4 kg in the Met + GH group and by -2.7 +/- 2.9 kg in the Met + Placebo group (differences between the two groups: p = n. s.). Waist circumference decreased in both groups (Met + GH: 118 +/- 8 cm at baseline, 112 +/- 10 cm after 18 months; Met + Placebo: 114 +/- 7 cm vs. 109 +/- 8 cm; differences between the two groups: p = 0.096). In the Met + GH group, FPG increased significantly after 6 months (5.9 +/- 0.7 vs. 6.7 +/- 0.4 mmol/l; p = 0.005), but subsequently decreased to baseline levels (18 months: 5.8 +/- 0.2 mmol/l). FPG remained stable in the Met + Placebo group until 12 months had elapsed, and then slightly decreased (baseline: 6.2 +/- 0.3, 18 months: 5.5 +/- 0.6 mmol/l, p = 0.02). No significant changes were seen in either group regarding glucose and insulin AUC during oGTT or HbA (1c) levels. GDR at 18 months increased by 20 +/- 39% in Met + GH-group and decreased by -11 +/- 25% in the Met + Placebo group (differences between the two groups: p = 0.07). In conclusion, treatment of patients with metabolic syndrome and elevated FPG levels did not cause sustained negative effects on glucose metabolism or insulin sensitivity if given in combination with metformin. However, since our data did not show significant differences between the two treatment groups with respect to body composition or lipid metabolism, future studies including larger numbers of patients will have to clarify whether the positive effects of rhGH on cardiovascular risk factors that have been shown in patients with GH deficiency are also present in patients with metabolic syndrome, and are additive to the effects of metformin.

Aged↗
PubMed2004

Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation.

Serum calcitonin (CT) has become a very specific and sensitive marker for human medullary thyroid carcinoma (MTC), a neuroendocrine tumor affecting about 1 % of patients with nodular thyroid disease. MTC is characterized by early micrometastasis and a lack of curative non-surgical treatment, so that early diagnosis is desirable. Based on a systematic review of scientific evidence, we propose multidisciplinary consensus recommendations for the clinical use of CT in patients with nodular goiter. To exclude MTC, serum CT should be determined in patients with nodular thyroid disease, using a two-site CT immunoassay. If basal serum CT exceeds 10 pg/ml, CT should be analysed by pentagastrin stimulation testing, after renal insufficiency and proton pump inhibitor medication have been ruled out. As the risk for MTC is higher than 50 % in patients with stimulated CT values > 100 pg/ml, thyroidectomy is advised in these individuals. If stimulated CT exceeds 200 pg/ml, thyroidectomy and lymphadenectomy is strongly recommended. Pentagastrin-stimulated CT values < 100 pg/ml are associated with a low risk of MTC, or very rarely, non-metastasizing micro-MTC (size < 10 mm). Therefore, regular clinical and biochemical follow-up is the preferred treatment in such patients, unless thyroid malignancy is suspected otherwise.

Calcitonin↗
PubMed2004

Impact of disease activity on thyroid diseases in patients with acromegaly: basal evaluation and follow-up.

In patients with acromegaly, the exact incidence of thyroid disorders is still controversial and less is known about the impact of disease activity and successful treatment. To address this issue, we investigated 73 acromegalic patients (age 55 +/- 13 yr; mean +/- SD) by ultrasonography in comparison to an age-matched control group (54 +/- 1 yr) in the same moderate iodine deficient area (retrospective study). These non-acromegalic volunteers (n = 199) were examined in the same clinic during a thyroid screening test. At the time of examination, 52 (71.2 %) of the acromegalic patients were active, 17 (23.3 %) were cured, and 4 (5.5 %) were controlled with somatostatin analogues. The prevalence of goiter (normal range < 18 ml female, < 25 ml male) was significantly higher (82.2 %) in the mixed group of acromegalics (active, well controlled, cured; n = 73) and in the active group (90.4 %) than in the control group (n = 199, 18.1 %, p < 0.001). Thyroid nodules were found in 63.0 % of the mixed group of acromegalics and in 71.2 % of patients with active disease (33.1 % in controls, p < 0.001). (99 m)Tc scintigraphy revealed thyroid autonomy in 9/73 (12.3 %) and cold nodules in 19/73 (26.0 %) patients. Thyroid cancer was diagnosed in 4 (5.5 %) of acromegalic patients (3 papillary and 1 follicular carcinoma). We found a weak correlation between the disease duration and the initial thyroid volume (r = 0.54, p < 0.0056). Thirty-seven newly diagnosed acromegalics were followed over a period of 7.3 +/- 4.1 years. 5 (13.5 %) of these patients remained active, 8 (21.6 %) were controlled with somatostatin analogues, and 24 (64.9 %) were cured. The mean age, sex distribution, disease duration, prevalence of TSH-deficiency, and initial thyroid volume (46 +/- 11 ml in active, 42 +/- 7 ml in controlled, and 45 +/- 5 ml in cured patients) did not differ statistically between the three groups. In patients with active acromegaly, thyroid volume increased by 19.5 +/- 8.1 %. In contrast, thyroid volume decreased in the group of medically controlled and cured acromegalics (- 21.5 +/- 7.1 %; p < 0.005 and - 24.2 +/- 5.7 %; p < 0.002, respectively). No correlation was found between thyroid volume and TSH levels, levothyroxine and/or iodide administration neither in TSH sufficient nor in TSH insufficient patients. In conclusion, successful treatment of patients with active acromegaly decreases thyroid volume. Cold nodules and thyroid cancer frequently occur in acromegalic patients.

Acromegaly↗
PubMed2004

Subchronic effects of olanzapine on sleep EEG in schizophrenic patients with predominantly negative symptoms.

BACKGROUND: It is well known that sleep disturbance is an integral symptom of schizophrenia. In recent studies, a deficit of delta sleep has been observed in schizophrenic patients. Antipsychotic drugs with serotonin (5-HT2) receptor-antagonistic properties are considered to have delta sleep promoting effects. We have investigated the effects of subchronic olanzapine treatment on sleep EEG in schizophrenic patients. METHODS: The effects of administration of olanzapine (15 to 20 mg) on sleep were studied for four weeks in 10 male, drug-free patients suffering from schizophrenia with predominantly negative symptoms. Conventional sleep EEG parameters were investigated at baseline and after treatment with olanzapine for four weeks. Additionally, spectral power analysis of the EEG signal in distinct frequency bands was computed for different sleep stages. Psychopathology (PANSS, HAMD-17, HAMA) and side effects were assessed weekly. RESULTS: All patients improved, as measured by PANSS global scores. Compared to baseline, there was a significant improvement of parameters of sleep efficiency and an increase of delta sleep as well as REM sleep. Regarding spectral power values, no significant differences between baseline and treatment conditions were found. CONCLUSIONS: Sleep improvement was due to parameters of sleep efficiency and delta sleep, which may be related to serotonin antagonistic properties of olanzapine.

Adolescent↗
PubMed2004

Identification of the major proteins of the organic matrix of emu (Dromaius novaehollandiae) and rhea (Rhea americana) eggshell calcified layer.

1. The eggshell is a composite consisting of 95% calcite and an organic matrix. 2. While many proteins of the chicken eggshell matrix have already been identified, little is known about the matrix of other birds. 3. Isolation of the emu and rhea eggshell matrix and analysis of its major constituents showed that the predominant components were C-type lectin-like proteins related to those of ostrich, chicken and goose. 4. Serum albumin, vitelline membrane outer layer protein I (VMO-I) and the turpentine-induced acute phase serum protein 18-B were identified as minor components of the emu shell matrix. Both eggshell matrices also contained a novel proline- and alanine-rich protein. 5. Like ostrich, and unlike chicken and goose, both emu and rhea eggshell matrix contained two different C-type lectin-like proteins as major components, indicating that the occurrence of two proteins of this family may be widespread among ratites.

Amino Acid Sequence↗
PubMed2004

The human chorionic gonadotropin molecule from patients with trophoblastic diseases has a high thyrotropic activity but is less active in the ovary.

To examine the pathogenesis of hyperthyroidism in women with trophoblastic diseases, the biological activity of human chorionic gonadotropin (hCG) molecules in women with normal pregnancy (n = 85) and in women with trophoblastic diseases (vesicular mole, n = 30; and choriocarcinoma, n = 12) was compared. Hyperthyroidism (thyroid stimulating hormone (TSH) < 0.3 mIU/l) was observed more frequently in women with trophoblastic diseases. All the sera were then subjected to Chinese hamster ovary cells transfected with the human TSH receptor (CHO-hTSHr cells) and cAMP production was compared. Sera from the women with choriocarcinoma showed the highest cAMP production. Interestingly, significant correlation between serum hCG level and cAMP production in CHO-hTSHr cells was observed only in women with trophoblastic disease. All the sera were then applied to CHO cells transfected with hCG/luteinizing hormone (LH) receptor (CHO-hCG/LHr cells). In contrast to the findings with the TSH receptor, sera from the women with normal pregnancy showed the highest cAMP production in these cells. Correlation between serum hCG level and cAMP production in CHO-hCG/LHr cells was significant only in normal pregnancy. These results indicate that the hCG molecule from women with trophoblastic diseases displays enhanced thyrotropic activity.

Adolescent↗
PubMed2004

Immunohistochemical determination of somatostatin receptor subtypes 1, 2A, 3, 4, and 5 in various adrenal tumors.

While octreotide binds with high affinity to sst2a only, the new analogue SOM230 demonstrates high affinity for sstl, 3, and 5, in addition. We examined the immunohistochemical expression of somatostatin receptor subtypes (sst) in 7 pheochromocytomas (PHEO), 5 Conn adenomas (CONN), 9 Cushing adenomas (CUSH), 7 nonfunctioning tumors (NFA), and 4 adrenal carcinomas (CA). About one third of the PHEO were positive for sst1, 2a, and 5. Less than 30% of cells were stained in the majority of these tumors. Each of the PHEO expressed sst3 with more than 60% of cells stained. Two thirds of the NFA revealed positive staining for sst1, 2a, and 3 with less than 30% of cells affected. Sst5 was expressed in nearly all of the NFA with positive staining in 30-60% of tumor cells. Nearly all CUSH and CONN were positive for the subtypes evaluated. In the majority of these tumors, less than 30% of cells were positively stained. Fifty percent of CA expressed sst2a and 3 with positive staining in 30-100% of cells. None of them expressed sst1. Somatostatin receptors are expressed in adrenal tumors with a tumor-specific distribution pattern. This may offer new diagnostic and therapeutic possibilities.

Adenoma↗
PubMed2004

Insulin sensitivity and coronary vasoreactivity: insulin sensitivity relates to adenosine-stimulated coronary flow response in human subjects.

OBJECTIVE: Diabetes is associated with coronary microvasculature abnormalities and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under maximal vasodilation to basal flow and is a measure for coronary vasoreactivity. Insulin resistance is the central defect in the development of type 2 diabetes, preceding its onset by 10-20 years. Thus, the relationship between insulin sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim of the study was to investigate this relationship. DESIGN: Cross-sectional study. PATIENTS: The study population consisted of 18 nondiabetic subjects without coronary artery stenosis on coronary angiography. We excluded patients with structural heart disease or with conditions affecting CFR or insulin sensitivity such as low density lipoprotein (LDL)-cholesterol > or = 4.14 mmol/l, smoking, hypertension or obesity with a body mass index (BMI) > 28 kg/m(2). MEASUREMENTS AND RESULTS: CFR was 3.1 +/- 0.8 (range 1.7-4.8), as assessed by intracoronary Doppler measurements in the left anterior descending coronary arteries after adenosine stimulation. Intravascular ultrasound revealed zero to moderate coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was 7.5 +/- 2.9 mg/kg/min (range 2.2-12.6), as assessed by the hyperinsulinaemic-euglycaemic clamp test. Subjects with low CFR (< 3.0) had a significantly lower M-value than subjects with normal CFR (> 3.0) (6.0 +/- 2.5 vs. 9.0 +/- 2.5 mg/kg/min, P = 0.021). Univariate linear regression demonstrated a strong correlation between CFR and M-value (r = 0.76, P < 0.001). In multiple regression analysis, the significant association of CFR with M-value was independent of potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on intravascular ultrasound). Bootstrap analysis corroborated this finding. CONCLUSIONS: Whole-body insulin sensitivity relates to coronary vasoreactivity. Across a wide range of both insulin sensitivity and coronary flow reserve from markedly abnormal to normal values, an increase in insulin sensitivity appears to be associated with an increase in coronary flow reserve. Insulin resistance is therefore associated with coronary microvasculature abnormalities in nondiabetics.

Adenosine↗
PubMed2004

Thyroid associated ophthalmopathy: evidence for CD4(+) gammadelta T cells; de novo differentiation of RFD7(+) macrophages, but not of RFD1(+) dendritic cells; and loss of gammadelta and alphabeta T cell receptor expression.

AIM: To characterise periorbital immune cells (stages, kinetics) in active and inactive thyroid associated ophthalmopathy (A-TAO; I-TAO). METHODS: In orbital tissue cryosections of patients with A-TAO (n = 15), I-TAO (n = 11), and healthy controls (n = 14), adipose and fibrovascular areas were evaluated for MHC II(+) cells, CD45(+) total leukocytes, myeloid cells (CD33(+) monocytes; CD14(+) macrophages; mature RFD7(+) macrophages; RFD1(+) dendritic cells (DCs)), and lymphoid cells (CD4(+) T cells; alphabeta and gammadelta T cells; CD20(+) B cells). Results are expressed as medians and 5% confidence intervals. RESULTS: In fibrovascular septae, a surge of CD33(+) immigrants clearly correlating with disease activity generated significantly increased (p<0.05) percentages of CD14(+) and RFD7(+) macrophages. Intriguingly, CD4(+) cells were mostly gammadelta T cells, while alphabeta T helper cells were much less frequent. Successful treatment rendering TAO inactive apparently downregulates monocyte influx, macrophage differentiation, and T cell receptor expression. Similar trends were recorded for adipose tissue. Interestingly, RFD1(+) DCs were completely absent from all conditions examined. CONCLUSION: A-TAO coincides with periorbital monocyte infiltration and de novo differentiation of macrophages, but not DCs. The authors discuss a novel potential role for inflammatory CD4(+) gammadelta T cells in TAO. Successful treatment apparently downregulates orbital monocyte recruitment and effects functional T cell knockout.

Acute Disease↗
PubMed2004

Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly.

OBJECTIVES: Sleep apnoea has been consistently reported to occur in acromegaly. Both obstructive apnoeas, in which apnoeas are due to intermittent obstruction of the upper airways, as well as central apnoeas are known to occur. Because the relationship between disease activity and severity of sleep apnoea is currently unclear, we have performed a prospective study to address this issue. DESIGN AND METHODS: In 14 newly diagnosed patients with active acromegaly (eight females and six males; mean age 57+/-4 years; IGF-I 583+/-48 microg/l; GH 13.5+/-7.0 microg/l (means+/-s.e.m.)), tongue volume and signal intensity of the tongue were examined by magnetic resonance imaging and sleep apnoea was characterised by polysomnography before and after 6 months of treatment with octreotide acetate (Sandostatin LAR 10-30 mg every 4 weeks i.m.). RESULTS: The initial tongue volume was significantly higher in patients with acromegaly (151+/-9 ml; females 133+/-10 ml; males 172+/-10 ml) in comparison with the body mass index (BMI)- and age-matched healthy control group (97+/-5 ml, P<0.001; females 75+/-1 ml, P<0.001; males 120+/-3 ml, P<0.003). After treatment with octreotide, IGF-I was normalised within the age-adjusted normal range in 50% of the patients. In these patients, tongue volume significantly decreased (120+/-14 ml, P<0.05) in comparison with the persistent uncontrolled group of acromegalics (137+/-10 ml, P=not significant). Overall, tongue volume (128+/-8 ml, P<0.05) and the signal intensity ratio of the tongue decreased significantly after treatment with octreotide acetate (120+/-3 vs 105+/-3, P=0.003). The BMI-adjusted tongue volume correlated with IGF-I levels (r=0.60, P<0.002) and the disease duration (r=0.71, P=0.006). At baseline, 50% had obstructive sleep apnoea with a mean respiratory disturbance index (RDI) of >20/h (range 5.1-91.5) and no patient had central sleep apnoea. After 6 months of octreotide treatment, there was a 28+/-10% decrease in RDI. However, RDI did not correlate with IGF-I or GH levels, but correlated positively with BMI (r=0.58, P=0.001) and age (r=0.46, P=0.02). CONCLUSIONS: Obstructive sleep apnoea but not central sleep apnoea frequently occurs in patients with active acromegaly. Successful treatment with octreotide can decrease tongue volume, which may have benefits for coexisting sleep-disordered breathing.

Acromegaly↗
PubMed2004

[Problems and new developments in the management of Graves' disease: medical therapy].

Since no causative treatment of Graves' disease is available, symptomatic therapy has been derived from clinical studies (evidence class I and II). To date, conservative treatment still has a relapse rate of 30-50% that is most likely due to the heterogeneity of patients. There is no clear data about the duration of therapy necessary for the individual patient. Previous prospective randomised studies have evaluated prognostic parameters including the use of levothyroxine for relapse prevention. For an improved characterisation of the natural course of Graves' disease, the period after drug withdrawal was studied. As patients treated with high doses of antithyroid drugs (< 10 mg thiamazole) and patients with large goitres (< 50 ml) often develop hyperthyroidism, they make likely candidates for radioiodine therapy or surgery. Smoking is a very strong independent risk factor for relapse. A prospective multi-centre trial of the Thyroid Chapter of the German Endocrine Society (DGE-SSD) demonstrated that the basal TSH is the strongest prognostic parameter to predict relapse of hyperthyroidism with an accuracy of 75%. In the present study, levothyroxine supplementation did not prevent recurrent hyperthyroidism. In order to avoid hypothyroidism levothyroxine should only be used in combination with antithyroid drugs. In the face of the amelioration of nutritional iodine uptake in Germany, the application of low doses of antithyroid drugs will very likely no longer be sufficient. Future therapeutic recommendations will be based on selection criteria such as iodine supplementation, volume of goitre, smoking habits and basal TSH. used in combination with antithyroid drugs. In the face of the amelioration of nutritional iodine uptake in Germany, the application of low doses of antithyroid drugs will very likely no longer be sufficient. Future therapeutic recommendations will be based on selection criteria such as iodine supplementation, volume of goitre, smoking habits and basal TSH.

Clinical Trials as Topic↗
PubMed2003

[Acamprosate--new preclinical research aspects].

Acamprosate has been shown to be effective and safe in relapse prevention of alcoholism. The effect of acamprosate is explained by a functional antagonistic action on the N-methyl-D-aspartate (NMDA) receptor. Under normal physiological conditions acamprosate augments the functionality of the NDMA receptor, but it inhibits the overactivity of that receptor triggered by alcohol abuse and withdrawal. In addition, conditioned withdrawal phenomena that can lead to a relapse, are also reduced. The substance is not a substitution drug, nor does it have addictive potential. Moreover, it also has a neuroprotective action. Whether acamprosate has a role as a neuroprotective agent in humans needs to be investigated.

Acamprosate↗
PubMed2003

[Advances in the treatment of alcohol dependence: pharmacological relapse prevention].

The development and successful clinical examination of relapse preventing medications (so-called anti-craving substances) opens up completely new perspectives in the treatment of alcohol-dependent patients. This is especially important for the general practitioners since despite of improved psychosocial treatment of alcohol-dependent patients relapse rates after detoxification remain high. Since a few years, new medications reducing the relapse risk are available. In Germany acamprosate presently is the most important medication used for this indication. Compared with placebo treatment, approximatly twice as many patients remain abstinent under acamprosate one year after detoxification. The administration of the medication starts immediately after detoxification and supports the patient during the first months, when the relapse risk is especially high. The medical treatment, however, is not a replacement for a psychosocial treatment of the alcohol dependence, but should be accompanied by counselling and the attendance in self help groups.

Acamprosate↗